This proposal is focussed on two long term goals: (1) evaluating the taste worlds of tasters and nontasters of PROP and (2) understanding the ability of the taste system to produce normal real-world experience in the presence of extensive damage to the neural structures subserving taste. Taste thresholds for the bitter substance PROP (6-n-propylthiouracil) show a bimodal distribution leading to the designation 'tasters' for the more sensitive and 'nontasters' for the less sensitive. Family studies suggest that nontasting is a simple Mendelian recessive trait. Thus nontasters are homozygous for the recessive gene while tasters may be either heterozygous or homozygous for the dominant gene. The designation 'nontaster' vs 'taster' suggests that these are the important phenotypes but this may be incorrect. Tasters show considerable variability when they scale PROP. Some find PROP to be much more bitter than others do. One hypothesis to be tested in this project Is that the more appropriate division may be between supertasters (who may be homozygous dominants) and others. This hypothesis will be tested by psychophysical scaling and by a preliminary family study. Individuals with extensive damage to the taste system may have no subjective changes In taste experience. One hypothesis to explain this phenomenon is that there are inhibitory connections in the taste system. Thus if one nerve is damaged, it then fails to send its normal input to the brain but it also fails to send inhibition to other taste nerves. The output of those nerves is thus enhanced. An aim of this project is to test the release of inhibition hypothesis in two ways. First, anesthesia will be used to block specific loci and observe the effects on taste on other loci. Second, patients will be tested who have taste damage restricted to particular loci to see if they experience enhanced taste on other loci. Finally, particular qualities will be blocked on some loci (by Gymnema sylvestre, an herb that selectively affects sweetness and by adaptation) to test the possibility that the release of inhibition Is quality specific. Another factor in the failure of patients to notice partial taste damage concerns the ability to localize taste. This project will investigate localization illusions that permit taste to appear to come from areas that are known to be devoid of receptors. A new discovery has caused these two lines of research to converge. Nontasters are now thought to have fewer taste buds than tasters. One long-term goal of this research is to determine whether or not nontasters and those who have suffered partial taste losses are at special risk for devastating losses in the future. The capacity of the taste system to cope with damage is remarkable but It is not unlimited. The overall goal of this project is to determine those limits.